Analysis Argues That Egg Production Keeps Flu Vaccine Efficacy Low

By staff

The effectiveness for the next influenza vaccination might be as low as recent years, despite a new H3N2 formulation for the first time since 2015.

That’s according to a report published online by Clinical Infectious Diseases. Rice University researchers explain that the reduced effectiveness is caused by viral mutations related to vaccine production in eggs.

Rice uses a method, pEpitope, which was developed more than a decade ago, to quickly evaluate the effectiveness of proposed flu-vaccine formulations. The pEpitope process accounts for 77% of what affects vaccine efficacy in humans and has been determined in recent studies to be more effective than ferret tests, which are commonly used.

By measuring critical differences in the genetic sequences of flu strains, pEpitope accurately predicted vaccine efficacy rates for more than 40 years of flu records, including last two flu seasons in which vaccines offered only limited protection against the most widely circulating strain of influenza A, study authors pointed out.

“The vaccine has been changed for 2018-19, but unfortunately it still contains two critical mutations that arise from the egg-based vaccine production process,” explained Michael Deem, PhD, Rice’s John W. Cox Professor in Biochemical and Genetic Engineering and professor of physics and astronomy. “Our study found that these same mutations halved the efficacy of flu vaccines in the past two seasons, and we expect they will lower the efficacy of the next vaccine in a similar manner.”

While full efficacy data for the 2017-2018 flu season are still being compiled, pEpitope has predicted it will end up at about 19% against H3N2, the most common circulating virus in recent years versus about 20% the year before.

Efficacy of 20% means that 20% fewer vaccinated people will get the flu, compared to those remaining unvaccinated, the study clarifies.

The issue, according to the researchers, is that most flu vaccines are produced with a longstanding process that involves culturing viruses in hundreds of millions of chicken eggs. Influenza affecting humans often is difficult to grow in eggs, requiring vaccine producers to make compromises to produce enough egg-based vaccine in time for the fall immunization push.

“Very often there are egg adaptations,” Deem noted. “There were a couple of these in the vaccine strain the past two seasons that wound up making it a little bit different from the actual circulating virus strain.”

Coauthor Melia Bonomo, a doctoral student in applied physics, described the differences, stating, “In fact, it's pretty substantial. The original strain used as a reference for the vaccine was basically a perfect match to the dominant circulating strain, and the predicted efficacy would have been around 47%. We found that the mutations in two amino acids out of more than 300 in one key region of the hemagglutinin protein were enough to lower efficacy to 19% against all circulating strains.”

The research compared the efficacy of the egg-based vaccine with an experimental vaccine produced from insect cells via reverse genetics and found that the cell-based vaccine had a predicted efficacy of 47%, the average value of a perfectly matched H3N2 vaccine, Deem said.